The objective of this proposal is to develop an understanding of the functional interactions occurring between nerves and mast cells within central and peripheral airways. Experiments will be carried out to test the hypotheses that intramural nerves in isolated airways regulate the function of airway mast cells, and that mast cell associated inflammatory mediators influence neuroeffector transmission. Mast cell function in central airways will be investigated using human bronchi and guinea pig trachea and bronchi. The function of peripheral airway mast cells will be studied in isolated human airways 1-2 mm in diameter. Airway mast cell responses will be evaluated through the measurement of antigen-induced changes in smooth muscle tone and the quantification of released inflammatory mediators. Nerves in the airways will be stimulated by electric field stimulation or by stimulation of sympathetic or parasympathetic nerve trunks in the innervated guinea pig trachea preparation. Nerve function will be evaluated by measuring changes in smooth muscle tone and by examining the release of acetylcholine, norepinephrine, substance P, and vasoactive intestinal peptide. Mast cell response will be evaluated in the presence and absence of nerve stimulation and, conversely, nerve function will be evaluated in the absence and presence of antigen-induced mast cell activation. In addition, the effect of exogenous inflammatory mediators and neurotransmitters on nerve and mast cell function, respectively, will be studied. Results from the experiments will extend our knowledge of the communication existing between nerves and mast cells in the airways. Such information may provide important new insights into the pathophysiology of airway diseases such as bronchial asthma.